When performing histological assessments of specimens containing cells it is relevant to consider the quality of the staining before considering the histological findings in the specimen. Too little or too much staining as compared to a protocol may lead to incorrect evaluations of the specimen. In particularly if the specimen relates to tumor cells it may be crucial for the patient that the laboratory is capable of staining and evaluating the specimens correctly.
The human epidermal growth factor, commonly referred to as HER2, is amplified in approximately 18% to 20% of breast cancers. HER2 overexpression is associated with clinical outcomes in patients with breast cancer. Several studies have shown that agents that target HER2 are remarkably effective in both the metastatic and adjuvant settings. Trastuzumab (Herceptin; Genentech, South San Francisco, Calif.), a humanized monoclonal antibody, improves response rates, time to progression, and even survival when used alone or added to chemotherapy in metastatic breast cancer. Trastuzumab is also active as a single agent and was approved in 1998 by the US Food and Drug Administration for the treatment of metastatic disease.
The ASCO/CAP panel have issued guideline recommendations for HER2 testing in breast cancer, and it is recommended that HER2 status should be determined for all invasive (early stage or recurrence) breast cancer on the basis of one or more Her2 test results [1]. These guideline recommendations are adopted to a varying degree by different local national boards across the world.
In daily practice between 80 and 90 percent of primary HER2 testing in fx the United States is done with immunohistochemistry (IHC), while only 10 to 20 percent is done with FISH. Approximately 10 to 20 percent of IHC test results fall into the so-called “indeterminate” range, and those specimens are re-tested using FISH which is widely considered the Gold Standard. One reason for this practice is also price, where an IHC assay may cost $100 to $150, and a FISH assay may be double or triple that price
The ASCO/CAP guidelines were recently updated in November 2013 [2]. The Update Committee was concerned about false-negative and false-positive HER2 assessments. For example, a false-negative test result could lead to denial of trastuzumab treatment for a patient who could benefit from it. False-positive results could lead to the administration of potentially toxic, costly, and ineffective adjuvant HER2-targeted therapy for 1 year.
The purpose of the ASCO/CAP guidelines is to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker.
Despite efforts to provide detailed guidelines for improving the accuracy of the testing of HER2 protein expression, numerous reports of variability in interpretation have raised uncertainty about the reliability of results.